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- Title
Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction.
- Authors
Merx, Marc; Gorressen, Simone; Sandt, Annette; Cortese-Krott, Miriam; Ohlig, Jan; Stern, Manuel; Rassaf, Tienush; Gödecke, Axel; Gladwin, Mark; Kelm, Malte
- Abstract
Nitric oxide (NO) derived from endothelial NO synthase (NOS3) plays a central role in myocardial ischemia/reperfusion (I/R)-injury. Subsets of circulating blood cells, including red blood cells (RBCs), carry a NOS3 and contribute to blood pressure regulation and RBC nitrite/nitrate formation. We hypothesized that the circulating blood born NOS3 also modulates the severity of myocardial infarction in disease models. We cross-transplanted bone marrow in wild-type and NOS3 mice with wild-type mice, producing chimeras expressing NOS3 only in vascular endothelium (BC−/EC+) or in both blood cells and vascular endothelium (BC+/EC+). After 60-min closed-chest coronary occlusion followed by 24 h reperfusion, cardiac function, infarct size (IS), NO levels, RBCs NO formation, RBC deformability, and vascular reactivity were assessed. At baseline, BC−/EC+ chimera had lower nitrite levels in blood plasma (BC−/EC+: 2.13 ± 0.27 μM vs. BC+/EC+ 3.17 ± 0.29 μM; * p < 0.05), reduced DAF FM associated fluorescence within RBCs (BC−/EC+: 538.4 ± 12.8 mean fluorescence intensity (MFI) vs. BC+/EC+: 619.6 ± 6.9 MFI; *** p < 0.001) and impaired erythrocyte deformability (BC−/EC+: 0.33 ± 0.01 elongation index (EI) vs. BC+/EC+: 0.36 ± 0.06 EI; * p < 0.05), while vascular reactivity remained unaffected. Area at risk did not differ, but infarct size was higher in BC−/EC+ (BC−/EC+: 26 ± 3 %; BC+/EC+: 14 ± 2 %; ** p < 0.01), resulting in decreased ejection fraction (BC−/EC+ 46 ± 2 % vs. BC+/EC+: 52 ± 2 %; * p < 0.05) and increased end-systolic volume. Application of the NOS inhibitor S-ethylisothiourea hydrobromide was associated with larger infarct size in BC+/EC+, whereas infarct size in BC−/EC+ mice remained unaffected. Reduced infarct size, preserved cardiac function, NO levels in RBC and RBC deformability suggest a modulating role of circulating NOS3 in an acute model of myocardial I/R in chimeric mice.
- Subjects
BLOOD circulation; NITRIC-oxide synthases; MYOCARDIAL infarction; LEFT heart ventricle diseases; ENDOTHELIAL cells; CORONARY disease; REPERFUSION injury
- Publication
Basic Research in Cardiology, 2014, Vol 109, Issue 1, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-013-0398-1